Regenerative medicine technology tBiomedical engineering professors Devina Purmessur and Natalia Higuita-Castro are leading an interdisciplinary team at The Ohio State University to address an underlying cause of the pain, intervertebral disc (IVD) degeneration. They recently earned a one-year, $368,000 National Institutes of Health (NIH) R61 award to investigate novel minimally invasive and non-addictive therapies for low back pain.
According to Purmessur, director of the Spinal Therapeutics Lab and faculty member of the Spine Research Institute, most current surgical and non-surgical treatments focus on alleviating the pain. “The problem with focusing on just the pain, is that it doesn’t fix the disease,” she explained. “You’re just treating the symptoms.”
Therefore, the optimal therapy would target both structural restoration and pain reduction. For some time, Purmessur has questioned if diseased and deteriorating IVD cells could be coaxed to revert their phenotype back to original function and health. An opportunity to explore further came last year when she learned about another Ohio State biomedical engineering team’s breakthrough, tissue nanotransfection (TNT), that can convert skin cells into blood vessels and nerve cells.
“It started with a conversation with Natalia and Daniel (Gallego-Perez) about their work,” she said. “If they can take a cell and differentiate it into a completely different cell type, can we take a diseased cell and reverse it back to its healthy state through tissue engineering?”
Higuita-Castro believes they can. Their proposal employs a multi-disciplinary approach to determine the effects of non-viral delivery of developmental proteins, specifically transcription factors, to reprogram diseased IVD cells. It could potentially revolutionise spine surgery by providing clinicians with the ability to deliver a minimally invasive and non-addictive treatment of the underlying disease mechanisms in the operating room.
“Our delivery system is unique,” Higuita-Castro said. “We are using extracellular vesicles we have engineered as nanocarriers to carry a cocktail of reprogramming factors directly to the diseased cells.” Extracellular vesicles contain various biomolecules including DNAs, RNAs, proteins, and metabolites, and play a pivotal role in cell-to-cell communication.
Their cell-reprogramming concept has been proven in the lab, which the team published the Journal of Orthopaedic Research. Graduate research assistant Shirley Nina Tang was the lead author and performed the experimental work overseen by Purmessur and Higuita-Castro. The NIH-funded project will serve to further validate the technology and quantify the effects of non-viral delivery of transcription factors. The team will use engineered vesicles in controlled lab experiments with human patient-derived cells, and subsequently in rodent back pain models evaluating the animals’ spinal function and pain behaviour.
Since the intervertebral disc does not have a blood supply, traditional cell-based regenerative medicine techniques such as stem cell injection have encountered roadblocks in the spine. Purmessur explained that their approach is not introducing any other cell type into the body or removing cells to treat and reintroduce later.
“Whether during a back surgery or through minimally invasive techniques, the factors can be delivered to the cells where they are, giving them a kickstart to help the cells make healthy proteins and rebuild their extracellular matrix,” she said.
According to Higuita-Castro, another major advantage over other biological delivery systems, such as viruses, is that the extracellular vesicles are naturally-derived, which minimises inflammatory immune system response.
Based on the results of their in vitro and in vivo work, the research team plans to apply for additional funding to validate the treatment in a large animal model with chronic degenerative spine conditions. While a trial in a large animal model is a necessary step toward beginning human patient clinical trials, there also is significant potential benefit in reducing pain and suffering of companion animals currently seen in veterinary clinics.
Source: The Ohio State University College of Engineering
